Misc Pharm 1 Saved

competitive inhibitor of tyrosine hydroxylase

Tx for pheochromocytoma (decreases catecholamine synthesis by tumor by inhibiting rate-limiting enzyme of epi synthesis

short term: increased BP (sympathomimetic)
long term: decreased BP (sympatholytic; therapeutic use)

- uptaken into presynaptic SNS cells via NE reuptake pump
- blocks release of NE and displaces NE from vesicles

SE: orthostatic hypotension, diarrhea (causes excessive GI stimulation), inhibits ejaculation, sympathomimetic action esp. noted in pheo pts

decreases BP (sympatholytic)

highly lipid-soluble, so it can enter cells and storage vesicles
- inhibits ATP-dependent NE/DA uptake carrier in vesicles
- doesn't displace NE; vesicles just eventually run out

SE: DEPRESSION, sedation, lethargy, nightmares

MAO-B inhibitor

blocks tyramine degradation via monoamine oxidase, so that it can be converted to octopamine, which is an indirect sympathomimetic false NT

specifically blocks particular MAO responsible for degrading DA, so doesn't have dangers of hypertensive crisis of non-selective MAO inhibitors

Tx for HTN, depression, parkinson's

SE: wine & cheese syndrome

catecholamine

parenteral administration only

stimulates alpha, beta1, and beta2 receptors

Tx for acute hypersensitivity rxns, cardiac arrest, adjunct to local anesthetic (vasoconstricts, keeping LA in place longer)

SE: arrhythmias and MI, dramatic HTN and pulmonary edema

catecholamine

stimulates alpha1 and beta1 receptors

Tx for severe cases of shock (increases BP and increases HR)

catecholamine

stimulates beta1 and beta2 receptors

Tx for patient with HTN and CHF, or for asthma

SE: arrhythmias (so many that its use is VERY rare)

catecholamine neurotransmitter

increases pressure and rate of blood flow in the vasa recta, which increases the rate of exit of water in the vasa recta; since solute is still reabsorbed, this is carried away at a higher rate too, disrupting countercurrent exchange and inducing diuresis

stimulates renal dopamine receptors at low conc, then beta1 receptors, and then alpha1 receptors at increasing conc.

Tx for shock (excellent Tx b/c it increases renal blood flow while also increasing BP and HR)

alpha adrenergic agonist

alpha adrenergic agonist

Tx for nasal congestion or supraventricular tachycardia (SVT)

SE: horrible rebound congestion when used to treat nasal congestion

alpha adrenergic agonist

Tx for supraventricular tachycardia (SVT)

indirect sympathomimetic

displaces NE from vesicles in adrenergic nerve terminals

Tx for ADD in children (CNS stimulant)

selective beta2 adrenergic agonist

Tx for bronchospasm (i.e. asthma)

selective beta2 adrenergic agonist

Tx for bronchospasm or for premature labor (can delay labor by about two weeks)

selective beta2 adrenergic agonist

Tx for bronchospasm (asthma)

selective beta1 adrenergic agonist

Tx for CHF

irreversible alpha adrenergic antagonist

formerly used as Tx for HTN, but increased mortality

SE: epi reversal, dec BP, orthostatic hypotension, reflex tachycardia

competitive nonselective alpha adrenergic antagonist

formerly used as Tx for HTN, but caused increased mortality

SE: epi reversal, dec BP, orthostatic hypotension, reflex tachycardia

competitive selective alpha1 adrenergic antagonists

Tx for benign prostatic hypertrophy

SE: epi reversal, dec BP, orthostatic hypotension, reflex tachycardia

prototypical beta-blocker (first to come out)

had to give three times daily

Tx for angina, arrhythmias, HTN, hyperthyroidism, glaucoma, migraine, tremor, CHF

cardioselective beta blocker (blocks beta1 receptors)

one dose daily

Tx for angina, arrhythmias, HTN, hyperthyroidism, glaucoma, migraine, tremor, CHF

cardioselective beta blocker
(blocks beta1 receptors)

Tx for angina, arrhythmias, HTN, hyperthyroidism, glaucoma, migraine, tremor, CHF

beta blocker

increases LDL and total cholesterol

Tx for angina, arrhythmias, HTN (blocks renin release by blocking beta receptors on JG cells AND decrease CO), hyperthyroidism, glaucoma, migraine, tremor, CHF

beta blocker with partial agonist activity at beta receptors

in theory, good for asthmatics, but in practice turn out to be just as bad as other beta blockers

Tx for angina, arrhythmias, HTN, hyperthyroidism, glaucoma, migraine, tremor, CHF

alpha- and beta-blocker

in theory, should be a super antihypertensive, but clinically performs the same as the other beta-blockers

Tx for angina, arrhythmias, HTN, hyperthyroidism, glaucoma, migraine, tremor, CHF

beta-blocker

half-life of only 5-10 minutes

uses: decide whether or not to use a beta-blocker in a pt with MI (if it removes too much SNS stimulation, it will wear off shortly and you know not to use beta-blockers)

muscarinic agonist

Tx for glaucoma

muscarinic agonist

Tx for glaucoma

muscarinic agonist

Tx for GI hypomotility or for urinary retention

muscarinic antagonist

Tx for muscarinic overload

muscarinic antagonist

Tx for motion sickness

SE: mental confusion

antihistamine/antimuscarinic

dries up nasal secretions, etc.

Uses: OTC cold medication

muscarinic antagonist

reduced CNS effects make it a more desirable pre-anesthetic than atropine (to decrease bronchial secretions which are triggered b/c of irritation by inhaled general anesthetics)

ganglionic blocker

Tx for malignant HTN

ganglionic blocker

Tx for malignant HTN

competitive inhibitor of acetylcholinesterase (AChE)

blocks the degradation of ACh in synaptic cleft

Uses: test for myasthenia gravis (has a very short half-life)

carbamate

competitive inhibitor of acetylcholinesterase (AChE)

blocks degradation of ACh in synaptic cleft

Tx for myasthenia gravis and for hypotonic GI tract

carbamate

competitive inhibitor of acetylcholinesterase (AChE)

blocks degradation of ACh in synaptic cleft

Tx for myasthenia gravis

carbamate

competitive inhibitor of acetylcholinesterase (AChE)

blocks degradation of ACh in synaptic cleft

Tx for myasthenia gravis

organophosphate

irreversible inhibitor of acetylcholinesterase (AChE)

blocks degradation of ACh in synaptic cleft

Uses: insecticide and nerve gas

prodrug form of paraoxon

organophosphate oxidized by mammals and insects

Uses: insecticide

prodrug form of malaoxon

organophosphate oxidized by insects only

Uses: more selective insecticide than parathion

organophosphate antidote

has a nucleophilic oxygen that attacks the phosphate of organophosphates and removes them from acetylcholinesterase (AChE)

Tx for acute organophosphate toxicity (useless against chronic low-level exposure)

barbiturate

increases sensitivity of GABA-gated chloride channels at low doses; imitates GABA (opens chloride channels independently) and inhibits Glu release at high doses

Tx for grand mal and simple partial seizures

DO NOT USE FOR PETIT MAL SEIZURES

deoxybarbiturate precursor of phenobarbital and phenyethylmalonamide

Tx for grand mal and simple partial seizures

DO NOT USE FOR PETIT MAL SEIZURES

succinimide anticonvulsant

blocks T-type calcium channels

DOC for petit mal seizures

anticonvulsant

prolongs inactivation state of V-gated Na channels

DOC in partial seizures
Tx for depression patients refractory to or intolerant of lithium

benzodiazepine anticonvulsant; spasmolytic

- potentiates GABA at GABA-A receptors in the brain (anticonvulsant ability)
- enhances GABA-mediated presynaptic inhibition of Ia afferent fibers of spinal cord (spasmolytic ability)

quick onset with little effect on respiration

Tx for status epilepticus (esp. Grand mal) and for relief of muscle tension

benzodiazepine anticonvulsant

potentiates GABA at GABA-A receptors

long-acting with good efficacy against petit mal seizures

anticonvulsant

prolongs inactivation state of V-gated Na channels AND inhibits T-type Ca channels

given as a sodium salt (divalproex sodium) to reduce GI upset

Tx for petit mal, absence, and tonic-clonic seizures
Tx for depression patients refractory to or intolerant of lithium

hydantoin anticonvulsant

prolongs inactivation state of V-gated Na channels

Tx for grand mal and partial seizures (one of the most effective)

SE: hirsutism, gingival hyperplasia, ataxia

anticonvulsant

increases [GABA] in the CNS by an unknown mechanism

Tx for partial seizures (combined with other anti-epileptic drugs)

few side effects

new antiepileptic drug

Tx for partial and tonic-clonic seizures (used as an adjunct)

new antiepileptic drug

Tx for partial seizures

N-methyl-D-aspartate (NMDA) receptor antagonist

prevents/slows further cell damage caused by elevated intraneuronal calcium concentrations (NMDA receptor acts as a ligand- and voltage-gated calcium channel; it must have Glu and Gly bound AND have the membrane depolarized - which releases magnesium that blocks the channel - in order to open

Tx for alzheimer's disease

cholinesterase inhibitor

offsets the loss of presynaptic cholinergic function and therefore slows decline of memory as well as decline of ability to perform normal daily tasks (since cholinergic deficits have been linked to Alzhemer's disease)

Tx for Alzheimer's disease, but requires intact cholinergic neurons to be effective

designer drug of abuse

in dopaminergic neurons, MAO converts it to a metabolite that inhibits mitochondrial energy metabolism and produces parkinson-like symptoms

indirect-acting sympathomimetic

Tx for ADD

- tolerance develops for anoretic, euphoric, and lethal effects
- abstinence causes fatigue and sleep
- SE: HTN, tachycardia, arrhythmias, mydriasis

CNS stimulant drug of abuse
- can lead to psychosis (psychotomimetic)
- treat with neuroleptics

indirect-acting sympathomimetic

Tx for ADD

- tolerance develops for anoretic, euphoric, and lethal effects
- abstinence causes fatigue and sleep
- SE: HTN, tachycardia, arrhythmias, mydriasis

CNS stimulant drug of abuse
- active ingredient in "bath salts"
- can lead to psychosis (psychotomimetic)
- treat with neuroleptics

CNS stimulant

blocks reuptake of 5-HT, NE and DA by uptake pump of presynaptic adrenergic neurons

freebasing = converting cocaine HCl salt bought on the street to a free base with addition of bicarb to alkalinize

SE: arrhythmias (try beta-blockers for Tx), seizures (try antiepileptic drugs for Tx)

hallucinogen (drug of abuse)

- causes frank hallucinations in small doses
- causes depersonalization, panic rxns, acute paranoia, depression, suicidal tendencies, flashbacks
- can cause emergence of underlying mental illness
- linked with PTSD

SE: mydriasis, tachycardia, HTN (all mild)

hallucinogen

active ingredient in marijuana

produces strong psychological dependence, but otherwise very safe

metabolites are in urine for at least 2-3 weeks

hallucinogen (drug of abuse)

produces numbness & slurred speech at low doses; produces analgesia, hallucinations, psychosis, and coma at high doses

neuroleptics and hospitalization used to treat psychosis

hallucinogen (drug of abuse)

stimulant and psychedelic effects

CSF of chronic users has low levels of 5-HT

opioid narcotic

long half-life, with little sedative effect

Tx for narcotic dependence
- oral administration allows addict to come in for periodic dosing while receiving social rehab
- decreases severity of withdrawal symptoms

Tx for narcotic dependence
- relieves piloerection, intestinal cramps & anxiety related with narcotic abstinence

oral opiate antagonist

long duration of action

prevents addict from receiving a high from heroin/opiates

Uses: oral administration for use as a maintenance drug in Tx programs

opiate antagonist
- blocks delta, kappa, and mu receptors

short duration of action

Tx for narcotic OD
- can precipitate withdrawal in chronic abusers
- IV infusion
- watch pts carefully (opiate still present in blood binds receptors if naloxone wears off)

combination of levodopa and cabidopa

levodopa is a dopamine precursor and carbidopa is an inhibitor of peripheral aromatic amino acid decarboxylase
- required dose of levodopa can be decreased
- supplemental intake of B6 no longer affects efficacy of levodopa

Tx for Parkinson's disease (requires intact DA neurons for conversion of levdopa to DA)

dopamine precursor

crosses the blood-brain barrier, where dopamine itself does not

Interactions:
1) aromatic amino acid decarboxylase converts L-dopa to dopamine in the periphery; supplemental intake of vitamin B6 increases this reaction in the periphery, so you need a larger dose
2) COMT converts L-dopa into O-methyl-dopa, which is an inactive form that cannot enter the CNS

Tx for Parkinson's Disease
- MUST have intact DA neurons to convert L-dopa to DA
- almost always combined with carbidopa (sinemet)
- only provides relief for about five years b/c nigrostriatal neurons continue to degenerate

SE: psychosis, N/V (DA receptors in CNS and GI), arrhythmias (indirect sympathomimetic)

inhibitor of peripheral aromatic amino acid decarboxylase (cannot cross the blood-brain barrier, so no CNS inhibition of AAADC)

blocks conversion of L-dopa to dopamine in the periphery so that the majority of a dose can get into the CNS

Uses: decreases required dose of L-dopa necessary to treat Parkinson's disease by 50-60% and eliminates concerns about pyridoxine enhancing peripheral L-dopa metabolism

antiviral agent that increases dopamine output of nigrostriatal neurons

tolerance develops with repeated use

Tx for flare-ups of Parkinson's disease

antimuscarinic

Tx for Parkinson's syndrome caused by antipsychotics (NOT FOR PARKINSON'S DISEASE)

SE: dry mouth, constipation, mental confusion, etc.

DO NOT USE IN OLD PEOPLE

antimuscarinic

Tx for Parkinson's syndrome caused by antipsychotics (NOT FOR PARKINSON'S DISEASE)

SE: dry mouth, constipation, mental confusion, etc.

DO NOT USE IN OLD PEOPLE

dopamine agonist

easily crosses the blood-brain barrier

doesn't depend on intact nigrostriatal neurons, so have some efficacy in late stages of Parkinson's disease

Tx for Parkinson's disesae after L-dopa no longer works

dopamine agonist

easily crosses the blood-brain barrier

doesn't depend on intact nigrostriatal neurons, so have some efficacy in late stages of Parkinson's disease

Tx for Parkinson's disesae after L-dopa no longer works

catechol-O-methyltransferase (COMT) inhibitor

blocks formation of O-methyl-Dopa from L-dopa, so a decreased dose is needed

dopamine blockers (neuroleptics)

e.g. haloperidol or chlorpromazine

dopamine blocker and antimuscarinic

Tx for Huntington's Chorea and for hiccups

SE: sedation, hypotension (blockade of alpha1 receptors), dry mouth, constipation, and pseudopregnancy (no ovulation or menstruation, but hyperprolactinemia and galactorrhea; caused by blockade of FSH and LH with enhancement of prolactin release) - but few extra-pyramidal symptoms

blocks calcium release from channels in the SR of skeletal muscle

Tx for malignant syndrome of antipsychotics (stupor, fever, unstable BP) and for malignant hyperthermia caused by anesthetics

dopamine blocker (antipsychotic)

Tx for Huntington's Chorea and for severe agitation

SE: minimal sedation, mild antimuscarinic, high incidence of acute dystonia

available as a depot form (administered every three weeks)

new antipsychotic

blocks 5-HT receptors and all 5 DA receptors (only mildly blocks D2 receptors, so few extrapyramidal symptoms)

Tx for refractory schizophrenia

SE: strong sedation, antimuscarinic activity, hypotension, agranulocytosis (significant number of pts)

new antipsychotic

blocks 5-HT receptors and all 5 DA receptors (only mildly blocks D2 receptors, so few extrapyramidal symptoms)

SE: sedation and hypotension (no agranulocytosis like clozapine)

new antipsychotic

blocks 5-HT receptors and all 5 DA receptors (only mildly blocks D2 receptors, so few extrapyramidal symptoms)

SE: sedation and hypotension (no agranulocytosis like clozapine)

new antipsychotic

blocks 5-HT receptors and all 5 DA receptors (only mildly blocks D2 receptors, so few extrapyramidal symptoms)

SE: sedation and hypotension, EPS at higher doses (no agranulocytosis like clozapine)

available as a depot form (administered every three weeks)

new antipsychotic

blocks 5-HT receptors and all 5 DA receptors (only mildly blocks D2 receptors, so few extrapyramidal symptoms)

SE: sedation and hypotension, EPS at higher doses (no agranulocytosis like clozapine)

new antipsychotic

partial agonist of D2 dopamine receptor

dopamine stabilizer - inhibits stimulation of mesolimbic pathways (lessening of positive symptoms), but stimulates mesocortical pathways ( lessening of negative symptoms)

SE: minimal sedation and hypotension

old antipsychotic

dopamine antagonist

Tx for schizophrenia

SE: extrapyramidal symptoms seen readily

available as a depot form (administered every three weeks)

spasmolytic

GABA receptor agonist that causes increased chloride influx and hyperpolarizes neurons

SE: sedation (not as bad as benzos)

spasmolytic drug

SE: sedation

spasmolytic drug

SE: sedation

tertiary amine tricyclic antidepressant (TCAD)

blocks NE and 5-HT reuptake

broken down in liver (N-methyl group is removed) to nortriptyline

Tx for chronic pain of a neural origin and depression

SE: strong sedation, strong anti-muscarinic effects, hypotension, cardiac effects

secondary amine tricyclic antidepressant (TCAD)

blocks NE reuptake

metabolite of amitriptyline (N-methyl group removed by liver)

Tx for depression

SE: sedation, anti-muscarinic effects, hypotension, cardiac effects (weaker than with amitriptyline)

aka prozac

SSRI - blocks 5-HT reuptake

Tx for depression or for OCD

SE: agitation, restlessness, N/V, headache, sexual dysfunction (NO sedation, anti-muscarinic effects, hypotension, or cardiac effects)

SSRI - blocks 5-HT reuptake

Tx for depression

SE: N/V, headache, sexual dysfunction (NO sedation, anti-muscarinic effects, hypotension, or cardiac effects)

aka paxil

SSRI - blocks 5-HT reuptake

Tx for depression

SE: N/V, headache, sexual dysfunction (NO sedation, anti-muscarinic effects, hypotension, or cardiac effects)

aka zoloft

SSRI - blocks 5-HT reuptake

Tx for depression

SE: N/V, headache, sexual dysfunction (NO sedation, anti-muscarinic, hypotension, or cardiac effects)

SNRI - blocks 5-HT and NE reuptake

Tx for depression or chronic pain of neural origin

SE: NO sedation, anti-muscarinic, hypotension, or cardiac effects

aka effexor

SNRI - blocks 5-HT and NE reuptake

Tx for depression or chronic pain of neural origin

SE: NO sedation, anti-muscarinic effects, hypotension, or cardiac effects

aka wellbutrin or zyban

atypical antidepressant

Uses: smoking cessation (3-month treatment program)

SE: seizures at doses > 450mg, so must limit doses

atypical antidepressant

blocks post-synaptic 5-HT receptors and blocks NE reuptake

Tx for depressed pts with insomnia

SE: strong sedation (NO anti-muscarinic effects, hypotension, or cardiac effects

atypical antidepressant

blocks serotonin receptors and blocks serotonin reuptake

Tx for insomnia (sleeping pill)

SE: strong sedation, but no anti-muscarinic effects (which makes it a good sleeping pill), prolonged erection

"mood-stabilizing" ion with unknown mechanism of action

Tx for manic depression and unipolar depression

VERY narrow therapeutic window, so give multiple daily doses in extended release form to avoid peaks
- diuretics and low Na diet increase proximal reabsorption and may lead to toxic levels

SE: nausea, diarrhea, drowsiness, polyuria, polydipsia, wt gain at low doses; mental confusion, hyperreflexia, gross tremor, seizures, and death at high doses

phenanthrene

strong mu-opioid receptor agonist

tolerance & dependence develop with prolonged use (up-regulation of CREB increases intracellular [cAMP])

high risk of addiction/abuse

CNS effects: analgesia, euphoria, sedation, respiratory depression, cough suppression, miosis
peripheral effects: constipation, bronchial constriction, smooth muscle contraction

Tx for SOB associated with acute pulmonary edema or for severe pain

phenanthrene

strong mu-opioid receptor agonist

tolerance & dependence develop with prolonged use (up-regulation of CREB increases intracellular [cAMP])

high risk of addiction/abuse

CNS effects: analgesia, euphoria, sedation, respiratory depression, cough suppression, miosis
peripheral effects: constipation, bronchial constriction, smooth muscle contraction

Tx for severe pain

phenanthrene

strong mu-opioid receptor agonist

tolerance & dependence develop with prolonged use (up-regulation of CREB increases intracellular [cAMP])

high risk of addiction/abuse

CNS effects: analgesia, euphoria, sedation, respiratory depression, cough suppression, miosis
peripheral effects: constipation, bronchial constriction, smooth muscle contraction

Tx for severe pain

phenylheptylamine

strong mu-opioid receptor agonist

CNS effects: analgesia, euphoria, sedation, respiratory depression, cough suppression, miosis
peripheral effects: constipation, bronchial constriction, smooth muscle contraction

longer half-life than morphine, but otherwise very similar

Tx for detoxification of heroin addicts

phenylpiperidine

strong opiate receptor agonist

High addiction/abuse potential

Tx for severe pain

SE: metabolites build up with poor renal fcn and cause seizures (only use if person has other allergies)
CNS effects: analgesia, euphoria, sedation, respiratory depression, cough suppression, miosis
peripheral effects: constipation, bronchial constriction, smooth muscle contraction

phenylpiperidine

strong mu-opioid receptor agonist

Uses: Tx for severe pain; preanesthetic or anesthetic (doesn't change TPR)

CNS effects: analgesia, euphoria, sedation, respiratory depression, cough suppression, miosis
peripheral effects: constipation, bronchial constriction, smooth muscle contraction

phenanthrene mild/moderate opiate agonist

moderate addiction/abuse potential

10% metabolized in the liver to form morphine, so oral form is much more potent than parenteral form (first-pass metabolism)

Tx for pain in combination with other drugs or for coughing

CNS effects: analgesia, euphoria, sedation, respiratory depression, cough suppression, miosis
peripheral effects: constipation, bronchial constriction, smooth muscle contraction

phenanthrene mild/moderate opiate agonist

Tx for pain in combination with other drugs (e.g. acetaminophen)

CNS effects: analgesia, euphoria, sedation, respiratory depression, cough suppression, miosis
peripheral effects: constipation, bronchial constriction, smooth muscle contraction

synthetic mild/moderate mu-opioid receptor agonist

low addiction/abuse potential b/c an active metabolite contributes largely to the analgesic effect which causes delayed onset without a rush (not even a scheduled drug b/c abuse potential is so low)

Tx for pain (just a little stronger than NSAIDS)

CNS effects: analgesia, euphoria, sedation, respiratory depression, cough suppression, miosis
peripheral effects: constipation, bronchial constriction, smooth muscle contraction

mixed opiate receptor agonist/antagonist

available in combination with naloxone to prevent abuse (if taken orally, naloxone is metabolized by liver; if injected, naloxone blocks action of pentazocine)

Tx for pain

CNS effects: analgesia, euphoria, sedation, respiratory depression, cough suppression, miosis
peripheral effects: constipation, bronchial constriction, smooth muscle contraction

mu-opioid receptor antagonist
kappa-opioid receptor agonist

low abuse potential b/c kappa receptor causes dysphoria

high dependence liability, so hard to withdraw

Tx for pain

CNS effects: analgesia, euphoria, sedation, respiratory depression, cough suppression, miosis
peripheral effects: constipation, bronchial constriction, smooth muscle contraction

dextrorotatory stereoisomer of a methylated derivative of the opiate levorphanol

no analgesic effect, no addiction liability

as good as codeine without the risks

Uses: OTC cough medication

partial agonist of opioid receptors

Tx for pain
- can precipitate withdrawal in chronic opiate users

CNS effects: analgesia, euphoria, sedation, respiratory depression, cough suppression, miosis
peripheral effects: constipation, bronchial constriction, smooth muscle contraction

arachidonic acid -(COX)-> PGG2 -(prostacyclin synthetase in vascular endothelium)-> PGI2

causes vasodilation and inhibits platelet aggregation

arachidonic acid -(COX)-> PGH2 -(thromboxane synthetase in platelets)-> TXA2

causes vasoconstriction and stimulates platelet aggregation

irreversible COX inhibitor (acetylates COX; unique b/c it's irreversible)
- anti-inflammatory effects from inhibition of COX2
- analgesic effect from depression of subcortical pain stimuli
- antipyretic effect from depression of PGE2 in hypothalamus
- antiplatelet effects from irreversible blockade of TxA2

blocks synthesis of PGI2 and TXA2, but PGI2 production recovers more quickly b/c endothelial cells have DNA and can synthesize more COX whereas platelets don't/can't

absorbed in stomach and small intestine (acidic environment maintains large fraction in nonionized form)

Uses: low dose for prophylaxis of stroke/MI (incidence dec. by 15%); high dose for headaches/pain relief

SE: CNS symptoms, Reye's syndrome (high ICP -> death), decreased renal blood flow (b/c PGs usually vasodilate), GI irritation/ulceration (PGs are protective in stomach)
TOXICITY: metabolic acidosis (uncouples ox-phos in mito, which increases CO2), fever, dehydration, coma, vasomotor collapse, renal/respiratory failure

phosphodiesterase inhibitor

blocks cAMP degradation in platelets so that cAMP/PKA-mediated inhibition of platelet activation is increased

Tx for prophylaxis of stroke/MI in combination with low dose aspirin (not very useful alone)

oral administration

blocks ADP binding to platelets so platelet activation is inhibited (similar to ticlopidine, but no risk of neutropenia)

Tx for prophylaxis of stroke/MI (little/no advantage over aspirin)

oral administration

anti-gpIIb/IIIa complex monoclonal antibody

prevents fibrinogen binding to and subsequent fibrin cross-linking of platelets

IV administration

Tx for halting MI/stroke in progress (little/no advantage over aspirin)

competitive inhibitor of gpIIb/IIIa receptor (mimics arg-gly-asp sequence of fibrinogen)

prevents fibrinogen binding to platelets, so cross-linking cannot occur

IV administration

Tx for halting MI/stroke in progress (little/no advantage over aspirin)

competitive inhibitor of gpIIb/IIIa receptor (mimics arg-gly-asp sequence of fibrinogen)

prevents fibrinogen binding to platelets, so cross-linking cannot occur

IV administration

Tx for halting MI/stroke in progress (little/no advantage over aspirin)

anticoagulant

binds thrombin and prevents it from activating coagulation factors as well as from binding to/activating platelets (inhibits platelet aggregation)

Tx for prophylaxis of DVT in pts with history of heparin-induced thrombocytopenia (HIT)
- MUST monitor pt's PTT because it interferes with the coagulation cascade

SE: greater bleeding risk than heparin alone

anticoagulant

binds thrombin and prevents it from activating coagulation factors as well as from binding to/activating platelets (inhibits platelet aggregation)

Tx for prophylaxis of DVT in pts with history of heparin-induced thrombocytopenia (HIT)
- MUST monitor pt's PTT because it interferes with the coagulation cascade

SE: greater bleeding risk than heparin alone

anticoagulant mucopolysaccharide consisting of variable number of repeating disaccharides (which determine the anticoagulant ability)

binds tightly to antithrombin III and causes conformational change which exposes an active site for rapid interaction with clotting factor proteases (Xa & thrombin only if > 18 saccharide units long)

must be administered subQ or IV

dose adjusted and maintained so that PTT is 2-2.5 times control

Tx for prophylaxis of venous clots (prevents clot enlargement), esp. for prevention of clot formation in bed-ridden patients

SE: bleeding, thrombocytopenia (Abs are developed to the heparin molecule, and they then cross-react with heparin-like molecules on platelets)

heparin antagonist

has a positive charge that attracts the negative charge of heparin and prevents heparin-antithrombin III interaction

Tx for heparin overmedication/overdose

low molecular weight (fractionated) heparin

binds antithrombin III and causes conformational change which exposes an active site for rapid interaction with clotting factor proteases (Xa; NOT thrombin b/c not enough saccharide residues to stabilize thrombin-antithrombin III interaction)

administered subQ

dose determined based on pt's weight

prophylaxis of DVT in surgical pts
Tx for MIs or strokes in progress
***DON'T use in pts with hx of HIT***

SE: bleeding, thrombocytopenia (reduced incidence compared to unfractionated heparin)

**b/c thrombin is not disturbed, don't need to monitor PTT**

synthetic pentasaccharide selective factor Xa inhibitor

binds antithrombin III and induces a conformational change which inactivates Xa (the molecule is not long enough to stabilize the thrombin-antithrombin III interaction)

doses determined by pt's weight (very predictable, no need to monitor PTT)

Tx for prophylaxis of DVT/PE in pts with history of HIT
**hasn't been studied yet for Tx of MI/CVA**

oral anticoagulant

inhibits epoxide reductase which is responsible for converting vitamin K from the inactive (oxidized) form to the active (reduced) form; since vitamin K is essential in the gamma-carboxylation of coagulation factors II, VII, IX, and X, blocking this enzyme decreases the available amount of functional coagulation factors (onset requires 5-10 days)

additional dietary vitamin K antagonizes warfarin, so pt needs to eat a constant amount of green, leafy vegetables

metabolized by cytochrome P450
- acute alcohol ingestion decreases metabolism, resulting in increasesed anticoagulation

Tx for long-term prophylaxis of MI/stroke
- dosing based on PT/INR

SE: bleeding

pt shouldn't take aspirin/NSAIDs or clopidogrel (antiplatelet effects potentiate bleeding)
if taking with amiodarone (to treat arrhythmias), decrease warfarin dose by 50%

aka phytonadione

necessary cofactor in the post-translational gamma-carboxylation of glutamate residues in coagulation factors II, VII, IX, and X; vitamin K is oxidized in this reaction and then reduced again by epoxide reductase to cycle again

reduced form is an antagonist of warfarin (which is a competitive inhibitor of epoxide reductase)

large amounts of reduced form found in green, leafy vegetables (pts on warfarin should eat constant amounts to avoid variability in anti-coagulation)

oral thrombin inhibitor

inhibits epoxide reductase (responsible for catalyzing the reduction of vitamin K to the active form; since vitamin K is necessary for gamma-carboxylation of coagulation factors II, VII, IX, and X, inhibition of this enzyme reduces the amount of functioning coagulation factors available)

advantages over warfarin:
- no necessary monitoring (neither INR or PTT)
- fewer drug interactions
- no food interactions

Tx for stroke prevention in pts with atrial fibrillation

SE: bleeding

thrombolytic drug

complexes with plasminogen and this complex converts uncomplexed plasminogen to plasmin; plasmin degrades fibrin and circulating fibrinogen

Tx for DVT (off-label), PE, and acute MI

SE: bleeding (b/c of dissolution of clots or b/c of a lytic state induced by degradation of fibrinogen)

blocks conversion of plasminogen to plasmin which increases clotting

Tx for some bleeding disorders or for OD of streptokinase/t-PA

thrombolytic that consists of streptokinase complexed with plasminogen

the active site of streptokinase is inhibited by addition of an acyl group, but the complex can still bind fibrin, which hydrolyzes the acyl group and then the streptokinase/plasminogen complex converts uncomplexed plasminogen to plasmin; plasmin degrades fibrin and circulating fibrinogen, which causes clot dissolution

Tx for DVT (off-label), PE, and acute MI

SE: bleeding (b/c of dissolution of clots or b/c of a lytic state induced by degradation of fibrinogen which is less than with streptokinase alone)

thrombolytic

greater specificity than streptokinase and urokinase b/c its main action (cleaving plasminogen to create plasmin) occurs after it binds to fibrin in clots (concentrates the plasmin just at the needed area)

expensive

easy to overshoot therapeutic dose (which is small) leading to a decrease in plasma fibrinogen
- just decrease dose

recombinant activated protein C (aPC)

antithrombotic properties: inactivates factors Va and VIIIa (with protein S); decreases production of PAI which causes an increase in plasmin leading to dissolution of clots
antiinflammatory properties: decreases production of IL-6 and TNF

Tx for septic shock with acute end-organ dysfunction

SE: bleeding and poverty

NSAID (reversible COX inhibitor)
- anti-inflammatory effects from inhibition of COX2
- analgesic effect from depression of subcortical pain stimuli
- antipyretic effect from depression of PGE2 in hypothalamus

Tx for acute gout (3 day Tx to avoid complications)

SE: abdominal pain, diarrhea, hemorrhage, pancreatitis

NSAID (reversible COX inhibitor)
- anti-inflammatory effects from inhibition of COX2
- analgesic effect from depression of subcortical pain stimuli
- antipyretic effect from depression of PGE2 in hypothalamus

propionic acid derivative

SE: decrease renal blood flow (PGs are usually vasodilating), GI irritation/ulceration (PGs are protective in stomach)

NSAID (reversible COX inhibitor)
- anti-inflammatory effects from inhibition of COX2
- analgesic effect from depression of subcortical pain stimuli
- antipyretic effect from depression of PGE2 in hypothalamus

propionic acid derivative

SE: decrease renal blood flow (PGs are usually vasodilating), GI irritation/ulceration (PGs are protective in stomach)

NSAID (reversible COX inhibitor)
- anti-inflammatory effects from inhibition of COX2
- analgesic effect from depression of subcortical pain stimuli
- antipyretic effect from depression of PGE2 in hypothalamus

better analgesic than anti-inflammatory drug

Tx for pain after surgery or from renal/gall stones (doesn't cause smooth muscle contraction like opioids)

SE: decrease renal blood flow (PGs are usually vasodilating), severe GI irritation/ulceration even with IV administration (PGs are protective in stomach)

NSAID (reversible COX inhibitor)
- anti-inflammatory effects from inhibition of COX2
- analgesic effect from depression of subcortical pain stimuli
- antipyretic effect from depression of PGE2 in hypothalamus

SE: decrease renal blood flow (PGs are usually vasodilating), GI irritation/ulceration (PGs are protective in stomach)

NSAID (reversible COX inhibitor)
- anti-inflammatory effects from inhibition of COX2
- analgesic effect from depression of subcortical pain stimuli
- antipyretic effect from depression of PGE2 in hypothalamus

SE: decrease renal blood flow (PGs are usually vasodilating), GI irritation/ulceration (PGs are protective in stomach)

NSAID (reversible COX inhibitor)
- anti-inflammatory effects from inhibition of COX2
- analgesic effect from depression of subcortical pain stimuli
- antipyretic effect from depression of PGE2 in hypothalamus

SE: decrease renal blood flow (PGs are usually vasodilating), GI irritation/ulceration (PGs are protective in stomach)

NSAID (reversible COX inhibitor)
- anti-inflammatory effects from inhibition of COX2
- analgesic effect from depression of subcortical pain stimuli
- antipyretic effect from depression of PGE2 in hypothalamus

SE: decrease renal blood flow (PGs are usually vasodilating), GI irritation/ulceration (PGs are protective in stomach)

NSAID (reversible COX inhibitor)
- anti-inflammatory effects from inhibition of COX2
- analgesic effect from depression of subcortical pain stimuli
- antipyretic effect from depression of PGE2 in hypothalamus

long half-life, so once-daily dosing

SE: decrease renal blood flow (PGs are usually vasodilating), GI irritation/ulceration (PGs are protective in stomach)

selective COX-2 inhibitor (only one that's important b/c others cause lots of trouble with thrombosis)
- anti-inflammatory effects from inhibition of COX2
- analgesic effect from depression of subcortical pain stimuli
- antipyretic effect from depression of PGE2 in hypothalamus
- has milder effects on GI and kidneys than do other NSAIDs
- no effects on platelets, so it can be used with warfarin

does not reduce inflammation better than other NSAIDs, but is very expensive

unknown mechanism of action

Tx for rheumatoid arthritis (RA)

corticosteroid

inhibits phospholipase A2, thereby inhibiting LT and PG production

initiate with a high dose, which gives prompt and dramatic relief, and then start a low daily dose to decrease side effects

SE: ulcers, diabetes, cushing's syndrome

methotrexate + prednisone

dihydroorotate dehydrogenase inhibitor

inhibits de novo pyrimidine - thymidine and cytidine - synthesis (b/c it depends on the oxidation of dihydroorotate to orotate, catalyzed by dihydroorotate dehydrogenase) which is essential for cell replication and clonal expansion after activation of lymphocytes

preferentially inhibits replication of B cells for unknown reason

Tx for RA (reduces signs/symptoms AND retards structural damage to joints)

decoy receptor for TNF (consists of extracellular portion of TNF receptor fused to the Fc region of human IgG1)

binds TNF-alpha and TNF-beta in the circulation and prevents their access to target tissues

Tx for RA

anti-TNFalpha monoclonal antibody (variable regions derived from mouse antihuman sequences; constant regions derived from human antibodies)

Tx for RA and for Crohn's disease

recombinant endogenous IL-1 receptor antagonist

blocks IL-1 binding to IL-1R, which inhibits stimulation of inflammation

supplements endogenous levels b/c they are not sufficient to compete for the IL-1R with the elevated levels of IL-1 in RA

nonopiate analgesic

removed from market b/c of prominent incidence of renal failure

acetaminophen is the active metabolite responsible for the analgesic effect

nonopiate analgesic
- no anti-inflammatory effects (very weak COX-2 inhibitor)
- similar to ASA in antipyretic and analgesic effects, but no anti-platelet effects (can use with warfarin)
- no GI bleeding/irritation
- no renal toxicity

derivative of phenacetin that is responsible for the analgesic effects

SE: hepatic toxicity if glucuronidation, sulfate conjugation, AND glutathione conjugation are saturated (OD)
- antidote = acetylcysteine

binds to and inhibits polymerization of tubulin, thereby preventing formation of microtubules
- decreases trafficking of phagocytosed particles to lysosomes
- decreases PMN release of chemotactic factors
- decreases LT synthesis
- decreases motility/adhesion of PMNs

Tx for gout only (resolve an acute attack)

SE: diarrhea (give to pt until diarrhea starts or flare-up stops)

indomethacin

colchicine (but it causes diarrhea)

competitive inhibitor of xanthine oxidase which leads to a decrease in uric acid production (hypoxanthine and xanthine build up, but they are relatively water soluble so they don't deposit in joints)

metabolized to alloxanthine by xanthine oxidase; alloxanthine is a non-competitive inhibitor of xanthine oxidase

Tx for chronic gout (prevents attacks, but worsens acute attacks in progress) (can be used with chemo to tx tumor lysis syndrome, which causes gout)

recombinant urate oxidase

enzyme found in birds which converts urate to allantoin; allantoin has good water solubility so it does not build up in the joints

Tx for chronic gout or can be used with chemo to tx tumor lysis syndrome (which causes gout)

uricosuric drug

blocks reabsorption of uric acid in the proximal tubule (and secretion, but since reabsorption > secretion the net effect is increased excretion); this increases renal clearance of plasma urate to decrease plasma uric acid levels

Tx for chronic gout (less common than allopurinol)

SE: renal stones (b/c of increased uric acid in renal tubules)
- solution: maintain urine pH at 6 (most uric acid kept in soluble form) and pt must drink a lot of fluid

a) contained in mast cells
- highest concentration in lung, skin, and mucous membranes
b) found outside of mast cells
- gastric mucosa and brain (NT)
c) effects: vasodilation, increased capillary permeability, bronchoconstriction, sensitization of nerve terminals (itching), inc. secretion of gastric acid, pepsin, and intrinsic factor, stimulates salivary glands
**all effects mediated by H1 receptors except GI effects (H2) and salivary glands (mACh)**
d) triggers for release: venoms & toxins, antigens (allergens), drugs (morphine)

mild antihistamine

Tx for prophylaxis of asthmatic or allergic bronchospasm or for anaphylaxis
- useless after mast cells have degranulated
- only mild effects in anaphylaxis b/c too many other autocoids are released with mast cell degranulation

nonsedating antihistamine
- too polar to cross blood-brain barrier

Tx for allergies (decreases itching, rhinitis, and edema)

nonsedating antihistamine
- too polar to cross blood-brain barrier

Tx for allergies (decreases itching, rhinitis, and edema)

nonsedating antihistamine
- too polar to cross blood-brain barrier

Tx for allergies (decreases itching, rhinitis, and edema)

antihistamine (H1 receptor antagonist)

Tx for rhinitis

antihistamine (H1 receptor antagonist)

Tx for motion sickness

SE: sedation

antihistamine (H1 receptor antagonist)

Tx for rhinitis or for insomnia

SE: mental confusion in elderly

antihistamine (H1 receptor antagonist)

Tx for N/V not related to motion sickness (many other causes)

SE: sedation

antihistamine (H1 receptor antagonist)

Tx for itching or motion sickness

antihistamine (H1 receptor antagonist)

long duration of action

Tx for dizziness or motion sickness

aka 5-hydroxytryptamine, 5-HT
a) distribution: more than 90% in gut (enterochromaffin cells); platelets take up 5-HT from gut; raphe nuclei of CNS
b) seven families of receptors
c) dominant role in migraine headaches

5-HT1D receptor agonist

causes vasoconstriction of cranial blood vessels (density of 5-HT1 receptors is high in cerebral vasculature, but low elsewhere)

Tx for migraines or cluster headaches (very efficacious, but expensive)
- subQ administration

5-HT3 receptor antagonist

Tx for nausea/vomiting

produced in zona glomerulosa of renal cortex and acts on the distal tubules and early collecting ducts of the nephron

synthesis/secretion is stimulated by inc. in potassium or angiotensin II (contribution of ACTH is minor)

actions:
1) upregulates & activates basolateral Na/K ATPase (stimulates redistribution of ATPase from cytosol to the basolateral membrane, as well as activating those already there and stimulating synthesis)
2) upregulates & activates ENaC (stimulates redistribution of ENaC from cytosol to apical membrane, as well as synthesis and activating those already on the apical membrane)
3) changes permeability of tight junctions
4) increases mito ATP production

Summary: increases NaCl reabsorption, potassium secretion/excretion and water retention; stimulates H+ secretion by intercalated cells

aka vasopressin/arginine vasopressin/AVP

secreted from posterior pituitary

synthesis/secretion is stimulated by dec. in blood volume (baroreceptors in veins, atria, carotids) and inc. in plasma oncotic pressure (osmoreceptors in hypothalamus)

actions:
1) increases permeability of distal tubule and collecting duct to water by causing insertion of aquaporins into the apical membrane (AVPR2 receptors)
2) increases permeability of inner medullary portion of collecting duct to urea (inc. reabsorption of urea)
3) causes vasoconstriction of peripheral arterioles (AVPR1 receptors)

carbonic anhydrase inhibitors

inhibit carbonic anhydrase in the proximal tubule (major site) and the distal tubule (minor site) which leads to decreased proximal reabsorption of bicarb and of Na

urinary electrolytes: inc. Na and K, big inc. in bicarb, dec. in H+ and NH4+ (FENa = 2-4%)

specific refractoriness = decreased response to drug that cannot be overcome by inc. of dose (requires bicarb to work, but concentrations of bicarb decrease so much that it can all be converted to CO2 and water without CA so body can conserve bicarb)

Tx for glaucoma (production of intraocular fluid requires CA) or for removal of small amounts of fluid (pre-menstrual swelling)

SE: specific refractoriness and metabolic acidosis

thiazide diuretics

inhibit NaCl symport on luminal membrane of the cortical ascending limb and distal tubule and have some ability to inhibit carbonic anhydrase

urinary electrolytes: inc. in bicarb and potassium, big inc. in Na and Cl (FENa = 10-12%)

different thiazides and also their doses differ based on lipophilicity of molecules (more lipophilic are reabsorbed more readily, so less is needed)

Tx mainly for HTN, but can be for mild edematous conditions (dec. preload in CHF pts) or for nephrogenic diabetes insipidus (increase Na excretion which prevents water being pulled from ICF and increases proximal fluid reabsorption to about 90%)

SE: nonspecific refractoriness, hyponatremia, hypokalemia, hypokalemic metabolic acidosis, hyperglycemia, ototoxicity (IV bolus too quickly), hypocalcemia, hyperuricemia, inc. in LDL/VLDL/TAG

Need creatinine clearance > 35 mL/min b/c thiazides decrease GFR and RBF slightly
- NSAIDs will decrease GFR and RBF further

thiazide-like diuretic (identical to thiazides except in structure)
- big difference = longer duration of action

inhibit NaCl symport on luminal membrane of the cortical ascending limb and distal tubule and have some ability to inhibit carbonic anhydrase

urinary electrolytes: inc. in bicarb and potassium, big inc. in Na and Cl (FENa = 10-12%)

different thiazides and also their doses differ based on lipophilicity of molecules (more lipophilic are reabsorbed more readily, so less is needed)

Tx mainly for HTN, but can be for mild edematous conditions (dec. preload in CHF pts)

SE: nocturia initially, nonspecific refractoriness, hyponatremia, hypokalemia, hypokalemic metabolic acidosis, hyperglycemia, ototoxicity (IV bolus too quickly), hypocalcemia, hyperuricemia, inc. in LDL/VLDL/TAG

Need creatinine clearance > 35 mL/min b/c thiazides decrease GFR and RBF slightly
- NSAIDs will decrease GFR and RBF further

thiazide-like diuretic (identical to thiazides except in structure)
- big difference = longer duration of action

inhibit NaCl symport on luminal membrane of the cortical ascending limb and distal tubule and have some ability to inhibit carbonic anhydrase

urinary electrolytes: inc. in bicarb and potassium, big inc. in Na and Cl (FENa = 10-12%)

different thiazides and also their doses differ based on lipophilicity of molecules (more lipophilic are reabsorbed more readily, so less is needed)

Tx mainly for HTN (effective in pts with dec. GFR; combine with furosemide), but can be for mild edematous conditions (dec. preload in CHF pts)

SE: nocturia initially, nonspecific refractoriness, hyponatremia, hypokalemia, hypokalemic metabolic acidosis, hyperglycemia, ototoxicity (IV bolus too quickly), hypocalcemia, hyperuricemia, inc. in LDL/VLDL/TAG

Need creatinine clearance > 35 mL/min b/c thiazides decrease GFR and RBF slightly
- NSAIDs will decrease GFR and RBF further

loop ("high ceiling") diuretic

inhibits Na/K/2Cl symporter on apical surface of thick ascending limb cells of loop of henle; inhibits Ca & Mg reabsorption through tight junctions

urinary electrolytes: huge inc. in Na and Cl, inc. K, H+ and NH4+; FENa = 20-30%

Tx for edematous conditions (dec. preload for CHF) or for hypercalcemia or for HTN

SE: hypokalemia (muscle weakness, digitalis toxicity), dehydration, nonspecific refractoriness, hyponatremia, hypokalemic metabolic acidosis, hyperglycemia, ototoxicity (IV bolus too quickly), hypomagnesemia/hypocalcemia, hyperuricemia (leading to gout)

loop ("high ceiling") diuretic

inhibits Na/K/2Cl symporter on apical surface of thick ascending limb cells of loop of henle; inhibits Ca & Mg reabsorption through tight junctions; only loop with some carbonic anhydrase inhibition ability

urinary electrolytes: huge inc. in Na and Cl, inc. HCO3 and K FENa = 20-30% (only loop that increases GFR and RBF)

Tx for edematous conditions (dec. preload for CHF) or for hypercalcemia or for HTN

SE: hypokalemia (muscle weakness, digitalis toxicity), dehydration, nonspecific refractoriness, hyponatremia, hypokalemic metabolic acidosis, hyperglycemia, ototoxicity (IV bolus too quickly), hypomagnesemia/hypocalcemia, hyperuricemia (leading to gout)

loop ("high ceiling") diuretic

inhibits Na/K/2Cl symporter on apical surface of thick ascending limb cells of loop of henle; inhibits Ca & Mg reabsorption through tight junctions

urinary electrolytes: huge inc. in Na and Cl, inc. K, H+ and NH4+; FENa = 20-30%

Tx for edematous conditions (dec. preload for CHF) or for hypercalcemia or for HTN

SE: hypokalemia (muscle weakness, digitalis toxicity), dehydration, nonspecific refractoriness, hyponatremia, hypokalemic metabolic acidosis, hyperglycemia, ototoxicity (IV bolus too quickly), hypomagnesemia/hypocalcemia, hyperuricemia (leading to gout)

aldosterone antagonist (competitive inhibitor of mineralocorticoid receptor) and K-sparing diuretic

decreases activity, migration, and synthesis of ENaC
decreases activity, migration, and synthesis of basolateral Na/K-ATPase
decreases permeability of tight junctions
increases ATP production of mitochondria
SUMMARY: blockade of Na reabsorption leads to dec. in K secretion (site of action: late DCT/early CD)

urinary electrolytes: inc. in Na and Cl, dec. in K, H+ and NH4+; no change in GFR/RBF; FENa = 3-4%

Tx for CHF (decreases mortality, independent of K-sparing ability)

SE: hyperkalemia, nonspecific refractoriness

K-sparing diuretic

inhibits Na channel on apical surface of principal cells of the late distal tubule and collecting duct, which results in decreased K secretion

urinary electrolytes: inc. in Na and Cl, dec. in K, H+ and NH4+; no change in GFR/RBF; FENa = 3-4%

uses: prevent K+ loss

SE: especially good at causing hyperkalemia, nonspecific refractoriness

K-sparing diuretic

inhibits Na channel on apical surface of principal cells of the late distal tubule and collecting duct, which results in decreased K secretion

urinary electrolytes: inc. in Na and Cl, dec. in K, H+ and NH4+; no change in GFR/RBF; FENa = 3-4%

uses: prevent K+ loss

SE: hyperkalemia, nonspecific refractoriness

polysaccharide osmotic diuretic

IV administration only (cannot cross lipid membranes)

restricted to ECF, so it pulls water out of cells (increases ECF at expense of ICF), and is then filtered but not reabsorbed so water is carried with it into the urine

Tx for high ICP and used in neurosurgery to "dry" the brain

vasopressin/ADH analog

binds ADH receptor which activates adenylate cyclase which converts ATP to cAMP which activates cAMP-dependent protein kinase; downstream effect is to increase apical ENaC expression, increase basolateral Na/K-ATPase, and increase ATP production in mito

administered as a nasal spray

Tx for vasopressin-sensitive diabetes insipidus (non-nephrogenic)